Presynaptic effects of 2-amnotetralins on striatal dopaminergic neurons

The present study evaluated whether 2-amino-5,6-dihydroxy-1,2,3,4,-tetrahydronapthalene (A-5,6 DTN) and its 6,7-dihydroxy isomer (A-6,7 DTN) had effects on striatal dopaminergic terminals in addition to their well known action as agonists on postsynaptic dopamine (DA)-receptors. The presynaptic effects of 2-aminotetralins were evaluated on rat striatal tissue slices prelabeled with [3H]DA. Both, A-5,6 and A-6,7 DTN enhanced the basal efflux of radioactive products in a concentration-dependent fashion. Benztropine (1μM) antagonized the releasing effects of low concentrations of both drugs (0.1-3.0μM). Apomorphine and A-5,6 DTN (alpha rotamers, trans conformation) were 3 to 5 times more potent than A-6,7 DTN (beta rotamer, trans conformation) in inhibiting rat striatal monoamine oxidase. This effect could account for the 50-fold greater potency of A-6,7 than A-5,6 DTN in enhancing the efflux of [3H]dihydroxyphenylacetic acid. A-5,6 DTN, A-6,7 DTN and apomorphine (0.3 μM each), reduced by 30% the depolarization elicited overflow of radioactive products. In summary, A-5,6 and A-6,7 DTN seem to enter DA-terminals and storage vesicles to accelerate the efflux of [3H]DA and 3H-dihydroxyphenylacetic acid and act upon presynaptic receptors to inhibit transmitter release. A greater selectivity for monoamine oxidase inhibiton was found with the alpha rotameric agents. The present study indicates that A-5,6 and A-6,7 DTN have marked presynaptic effects on rat striatal DA-containing neurons in addition to their well known effects as agonists on postsynaptic DA receptors.